Browsing by Subject "INFECTIOUS-DISEASE"

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  • Lilley, Thomas Mikael; Anttila, Jani Valtteri; Ruokolainen, Lasse (2018)
    White-nose syndrome (WNS), affecting multiple North American bat species during the hibernation period, is a highly pathogenic disease caused by the psychrophilic fungus Pseudogymnoascus destructans (Pd). Because the fungal pathogen persists in the hibernation site environment independently of the hosts, previous theory on spatial disease dynamics cannot predict WNS epidemics. However, the ability to understand factors contributing to the spread of white-nose syndrome (WNS) in North America is crucial to the management of infected and susceptible bat populations as well as the conservation of threatened and endangered bat species. Utilizing recent theory on environmental opportunistic pathogens, we modelled the effect of (a) landscape clustering, (b) environmental conditions in hibernacula and (c) microbial competition on the spread of WNS. We used available, already published data to construct and parameterize our model, which takes into account the spatial distribution of hibernation sites, temperature conditions in both the outside ambient and hibernation site environment, bat population dynamics, dispersal and infection by the pathogen, which also has its host-independent dynamics with the environment. We also consider the effect of outside-host competition between the pathogen and other micro-organisms on spatial disease dynamics. Our model suggests that pathogen loads accumulate in poorly connected hibernacula at short host dispersal, which can help found the epidemic. In contrast, invasion of the landscape is most successful at long host dispersal distances, with homogenous hibernation site distribution and heterogeneous between-hibernation site temperatures. Also, increasing the mean temperature across hibernacula increases fungal growth rate, leading to higher disease prevalence and faster invasion rate. Increasing spatial heterogeneity in hibernaculum temperatures results in the formation of disease hotspots in warmer hibernacula, facilitating more effective spread of the disease in the landscape. Cold-adapted competing microbes can prevent invasion, and therefore, overwintering in cold hibernacula increases probability of host survival. Sites that were suboptimal for overwintering prior to WNS may have importance in preventing local extirpations. Although the model is tailored for WNS, due to pressing need for results that can assist in planning conservation measures, these novel results can be broadly applied to other environmentally transmitted diseases. A is available for this article.
  • Penczykowski, Rachel M.; Parratt, Steven R.; Barres, Benoit; Sallinen, Suvi K.; Laine, Anna-Liisa (2018)
    Understanding how variation in hosts, parasites, and the environment shapes patterns of disease is key to predicting ecological and evolutionary outcomes of epidemics. Yet in spatially structured populations, variation in host resistance may be spatially confounded with variation in parasite dispersal and environmental factors that affect disease processes. To tease apart these disease drivers, we paired surveys of natural epidemics with experiments manipulating spatial variation in host susceptibility to infection. We mapped epidemics of the wind-dispersed powdery mildew pathogen Podosphaera plantaginis in five populations of its plant host, Plantago lanceolata. At 15 replicate sites within each population, we deployed groups of healthy potted 'sentinel' plants from five allopatric host lines. By tracking which sentinels became infected in the field and measuring pathogen connectivity and microclimate at those sites, we could test how variation in these factors affected disease when spatial variation in host resistance and soil conditions was minimized. We found that the prevalence and severity of sentinel infection varied over small spatial scales in the field populations, largely due to heterogeneity in pathogen prevalence on wild plants and unmeasured environmental factors. Microclimate was critical for disease spread only at the onset of epidemics, where humidity increased infection risk. Sentinels were more likely to become infected than initially healthy wild plants at a given field site. However, in a follow-up laboratory inoculation study we detected no significant differences between wild and sentinel plant lines in their qualitative susceptibility to pathogen isolates from the field populations, suggesting that primarily non-genetic differences between sentinel and wild hosts drove their differential infection rates in the field. Our study leverages a multi-faceted experimental approach to disentangle important biotic and abiotic drivers of disease patterns within wild populations.
  • Uusitalo, Ruut Jaael; Siljander, Mika; Culverwell, Christine Lorna; Mutai, Noah; Forbes, Kristian Michael; Vapalahti, Olli; Pellikka, Petri Kauko Emil (2019)
    Mosquitoes are vectors for numerous pathogens, which are collectively responsible for millions of human deaths each year. As such, it is vital to be able to accurately predict their distributions, particularly in areas where species composition is unknown. Species distribution modeling was used to determine the relationship between environmental, anthropogenic and distance factors on the occurrence of two mosquito genera, Culex Linnaeus and Stegomyia Theobald (syn. Aedes), in the Taita Hills, southeastern Kenya. This study aims to test whether any of the statistical prediction models produced by the Biomod2 package in R can reliably estimate the distributions of mosquitoes in these genera in the Taita Hills; and to examine which factors best explain their presence. Mosquito collections were acquired from 122 locations between January–March 2016 along transects throughout the Taita Hills. Environmental-, anthropogenic- and distance-based geospatial data were acquired from the Taita Hills geo-database, satellite- and aerial imagery and processed in GIS software. The Biomod2 package in R, intended for ensemble forecasting of species distributions, was used to generate predictive models. Slope, human population density, normalized difference vegetation index, distance to roads and elevation best estimated Culex distributions by a generalized additive model with an area under the curve (AUC) value of 0.791. Mean radiation, human population density, normalized difference vegetation index, distance to roads and mean temperature resulted in the highest AUC (0.708) value in a random forest model for Stegomyia distributions. We conclude that in the process towards more detailed species-level maps, with our study results, general assumptions can be made about the distribution areas of Culex and Stegomyia mosquitoes in the Taita Hills and the factors which influence their distribution.
  • Gillespie, Joseph J.; Phan, Isabelle Q. H.; Scheib, Holger; Subramanian, Sandhya; Edwards, Thomas E.; Lehman, Stephanie S.; Piitulainen, Hanna; Rahman, M. Sayeedur; Rennoll-Bankert, Kristen E.; Staker, Bart L.; Taira, Suvi; Stacy, Robin; Myler, Peter J.; Azad, Abdu F.; Pulliainen, Arto T. (2015)
    Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species (vir, vbh, and trw). In a unique case, most rickettsial species encode a T4SS (rvh) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably, while RvhB8-I dimerizes and is structurally similar to other VirB8 proteins, the RvhB8-II dimer interface deviates substantially from other VirB8 structures, potentially preventing RvhB8-I/RvhB8-II heterodimerization. For the rvh T4SS, the evolution of divergent VirB8 paralogs implies a functional diversification that is unknown in other T4SSs. Collectively, our data identify two different constraints (spatio-temporal for Bartonella trw and vir T4SSs and structural for rvh T4SSs) that mediate the functionality of multiple divergent T4SSs within a single bacterium. IMPORTANCE Assembly of multiprotein complexes at the right time and at the right cellular location is a fundamentally important task for any organism. In this respect, bacteria that express multiple analogous type IV secretion systems (T4SSs), each composed of around 12 different components, face an overwhelming complexity. Our work here presents the first structural investigation on factors regulating the maintenance of multiple T4SSs within a single bacterium. The structural data imply that the T4SS-expressing bacteria rely on two strategies to prevent cross-system interchangeability: (i) tight temporal regulation of expression or (ii) rapid diversification of the T4SS components. T4SSs are ideal drug targets provided that no analogous counterparts are known from eukaryotes. Drugs targeting the barriers to cross-system interchangeability (i.e., regulators) could dysregulate the structural and functional independence of discrete systems, potentially creating interference that prevents their efficient coordination throughout bacterial infection.